The Global Hypothesis for the proposed Phase II program is that Mesenchymal Stem Cells (MSCs) can be applied to models of tendon injury to provide improved and accelerated tissue regeneration in clinically meaningful situations. In Phase II we will explore two aspects of tendon repair in areas of important clinical applications. First, we will study repair in partial and complete Achilles tendon ruptures. Second, in another model system, we will study repair of the middle one-third patellar tendon gap created when this tissue is used as a donor graft for an anterior cruciate ligament (ACL) reconstruction. The Phase l results presented in this application demonstrate the feasibility of repairing tendon defects with a novel, proprietary MSC / biomatrix construct. Statistically significant positive biomechanical results of MSCs versus controls indicate the early stiffness and strength of these regenerated tendon-like structures following implantation into a rabbit Achilles tendon defect model. Histological data provide qualitative support of these findings. At the conclusion of Phase II, we will have sufficient data to progress towards FDA approval of an IND to commence human clinical studies. PROPOSED COMMERCIAL APPLICATION: We propose to apply a unique autologous cell -based therapy (MSC) to enhance significantly the rate and quality of repair in tendons. There are several hundred thousand incidences of these clinical situations we are seeking to improve with our model systems.